Persuant to 37 C.F.R. xc2xa7 1.71(e), Applicant note that a portion of this disclosure contains material which is subject to copyright protection. The coptright owner has no objection to the facsimile reproduction by anyone of the present document or patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.
Microfluidic devices generally provide reliable, accurate and high-throughput methods of performing diverse instrumental analyses, including various screening protocols and separation-based assays. Additionally, many microfluidic devices have been inexpensively incorporated as components of automated systems. Despite these attributes, certain limitations or inefficiencies exist, which, if overcome, would further enhance the utility of these devices and systems.
To illustrate, the phenomenon of spontaneous injection, while useful in certain microfluidic applications, can also be a limiting factor in others. It is typically caused by the surface tension present in a drop of fluid suspended from a capillary microchannel in certain devices. The surface tension tends to produce an inward pressure that forces (i.e., spontaneously injects) fluid into the capillary microchannel. Pressure variations due to spontaneous injection can generate flow rate fluctuations in a microfluidic device which can give rise to periodic fluctuations in the baseline signal of an associated detector. In turn, these baseline signal fluctuations can obscure detectable signals produced by assay components.
One method used to control the effects of spontaneous injection has been to alter certain geometric parameters, such as the diameter of a capillary microchannel. Another approach has been to maintain a relatively high dilution factor in such a microchannel. Both methods have also been used simultaneously. Additionally, temperature has been used to vary buffer viscosity in capillary microchannels. This approach can adversely impact the rates of certain biochemical assays.
Some microfluidic applications utilize microchannels simultaneously having both high hydrodynamic resistance and low electrical resistance, e.g., to deliver electrical fields to a reaction microchannel. Since hydrodynamic and electrical resistances have different design parameters related to channel depth, one technique for achieving these conditions has been to manufacture side microchannels shallower and wider than the reaction microchannel. However, microfluidic devices which include multiple microchannel depths can be more costly and difficult to fabricate than comparable single depth devices.
Accordingly, it would be advantageous to provide additional techniques for overcoming these limitations and inefficiencies, especially techniques for tailoring various characteristics of microfluidic devices during operation. The present invention provides additional methods and devices for controlling the effects of spontaneous injection and for regulating electric fields within microfluidic devices and systems.
The present invention provides methods and devices for inducing high bulk hydrodynamic resistance in microfluidic devices, e.g., to minimize the spontaneous injection signatures of the devices. The invention also relates to methods and devices for inducing low electrical resistance, in addition to high hydrodynamic resistance, in microfluidic devices, inter alia, for regulating electrical resistance within the devices.
The methods of inducing high bulk hydrodynamic resistance include providing a microscale cavity (e.g., a capillary microchannel) in the microfluidic device that includes a bulk viscosity enhancer disposed in the cavity. The microscale cavity optionally also includes a capillary microchannel that extends from the microfluidic device. The bulk viscosity enhancer effects an increase in bulk hydrodynamic resistance within the microscale cavity of the microfluidic device. Additionally, the bulk viscosity enhancer is, e.g., a polymer molecule that has a molecular weight of at least about one kilodalton. For example, bulk viscosity enhancers typically have molecular weights in the range of from about one kilodalton to about 1,000 kilodaltons, generally in the range of from about 5 kilodaltons to about 100 kilodaltons, e.g., about 50 kilodaltons. Suitable bulk viscosity enhancers include biocompatible polymers. For example, bulk viscosity enhancers optionally include one or more of: a single polymer, a mixture of polymers, a copolymer, a block copolymer, a polymer micellar system, an interpenetrating polymer network, a polymer gel, a polysaccharide (e.g., FICOLL(trademark), dextran, etc.), poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), poly(dimethylacryamide) (PDMA), derivatives thereof, or the like. Bulk viscosity enhancers are typically disposed in aqueous solutions.
Bulk hydrodynamic resistance in the microscale cavity in the device is regulated, e.g., by varying or selecting a concentration of the bulk viscosity enhancer disposed in the cavity, by varying or selecting a temperature within the microscale cavity, or both. The regulated bulk hydrodynamic resistance regulates spontaneous injection into the microscale cavity, e.g., during operation of the microfluidic device. Spontaneous injection is also optionally regulated by varying or selecting a concentration of a surfactant disposed in the microscale cavity. In another aspect of the invention, the regulated bulk hydrodynamic resistance regulates dispersion (e.g., slug dispersion) during fluid flow in the microscale cavity.
The methods of inducing high bulk hydrodynamic resistance optionally further include inducing low electrical resistance in the microfluidic device. The methods include, e.g., providing an electrolyte (e.g., a salt, a buffering ionic species, etc.) disposed in the microscale cavity (e.g., a microchannel). The diffusive mobility of the electrolyte is substantially unaffected by the increase in bulk hydrodynamic resistance within the microscale cavity, e.g., due to the small size of the electrolyte relative to the hydrodynamic radius of the bulk viscosity enhancer. As a result, low electrical resistance is induced in the microfluidic device. Furthermore, both the bulk viscosity enhancer and the electrolyte are optionally flowed in the microfluidic device using a fluid direction component that includes, e.g., a fluid pressure force modulator, an electrokinetic force modulator, a capillary force modulator, a fluid wicking element, or the like.
Bulk hydrodynamic resistance and electrical resistance in the microscale cavity in the microfluidic device are optionally individually or concomitantly regulated by varying or selecting a concentration of the at least one bulk viscosity enhancer and/or a concentration of the at least one electrolyte disposed in the cavity. Optionally, the bulk hydrodynamic resistance, the electrical resistance, or both, in the microscale cavity are regulated, e.g., during operation of the microfluidic device. Additionally, the methods optionally include providing a microchannel disposed in the microfluidic device that intersects and fluidly communicates with the microscale cavity. Regulating the electrical resistance in the at least one microscale cavity regulates electrical resistance in the at least one microchannel. Furthermore, the bulk viscosity enhancer and/or the electrolyte are optionally chosen to modify the electroosmotic velocity in the at least one microscale cavity.
The present invention also includes a device or system that includes a body structure that includes a microscale cavity (e.g., a capillary microchannel) extending from the body structure. The microscale cavity also includes a bulk viscosity enhancer disposed in the cavity. As mentioned, the bulk viscosity enhancer includes, e.g., a polymer molecule that includes a molecular weight of at least about one kilodalton. For example, bulk viscosity enhancers typically have molecular weights in the range of from about one kilodalton to about 1,000 kilodaltons, generally in the range of from about 5 kilodaltons to about 100 kilodaltons, e.g., about 50 kilodaltons. Additionally, preferred bulk viscosity enhancers include biocompatible polymers. Suitable bulk viscosity enhancers generally include one or more of: a single polymer, a mixture of polymers, a copolymer, a block copolymer, a polymer micellar system, an interpenetrating polymer network, a polymer gel, a polysaccharide, PEG, PVA, PDMA, derivatives thereof, or the like. Furthermore, bulk viscosity enhancers are typically disposed in aqueous solutions.
The device or system optionally further includes an integrated system that includes a computer or a computer readable medium that includes an instruction set for varying or selecting a concentration of the bulk viscosity enhancer disposed in the microscale cavity, for varying or selecting a temperature within the microscale cavity, or both. The microscale cavity optionally includes a capillary microchannel that extends from the microfluidic device. The varied or selected bulk viscosity enhancer concentration regulates bulk hydrodynamic resistance within the microscale cavity which, in turn, regulates spontaneous injection into the microscale cavity, e.g., during operation of the device. Optionally, the device or system also includes regulating spontaneous injection by varying or selecting a concentration of a surfactant disposed in the microscale cavity. In another aspect, the regulated bulk hydrodynamic resistance within the microscale cavity regulates dispersion (e.g., slug dispersion) during fluid flow in the microscale cavity.
The invention also includes a device or system that includes a body structure having a microscale cavity (e.g., a microchannel) fabricated in the structure in which the microscale cavity optionally includes a mixture of a bulk viscosity enhancer and an electrolyte (e.g., a salt, a buffering ionic species, or the like) disposed in the cavity. This device or system also optionally includes an integrated system that includes a computer or a computer readable medium that includes an instruction set. The instruction set varies or selects concentrations of the bulk viscosity enhancer and the electrolyte disposed in the microscale cavity to regulate bulk hydrodynamic resistance and electrical resistance within the microscale cavity.
The device also optionally includes a microchannel fabricated in the body structure. The microchannel intersects and fluidly communicates with the microscale cavity (which, in turn optionally comprises a microchannel) in which case, regulating the electrical resistance within the microscale cavity regulates electrical resistance in the microchannel. Furthermore, the bulk hydrodynamic resistance, the electrical resistance, or both, are optionally regulated within the microscale cavity during operation of the device.
The present invention also typically includes flowing the bulk viscosity enhancer and/or the electrolyte in the device or system using a fluid direction component that includes a fluid pressure force modulator, an electrokinetic force modulator, a capillary force modulator, a fluid wicking element, or the like.